Table 3.
Dose response of KI effects on mitochondrial oxygen consumption
| Drugs (fold of Cmax) | Glutamate/malate driven respiration | Succinate-driven respiration | ||
|---|---|---|---|---|
| State 4 | State 3 | State 4 | State 3 | |
| Sorafenib | ||||
| 10 | 5.00 ± 1.92* | 0.93 ± 0.34 | 3.34 ± 0.45* | 1.03 ± 0.19 |
| 5 | 3.69 ± 0.12* | 1.34 ± 0.04* | 1.03 ± 0.08 | 0.40 ± 0.01* |
| 2.5 | 4.92 ± 0.09* | 1.57 ± 0.06* | 1.43 ± 0.06* | 0.62 ± 0.05* |
| 1 | 2.55 ± 0.27* | 1.15 ± 0.09 | 1.50 ± 0.21* | 1.00 ± 0.10 |
| Regorafenib | ||||
| 10 | 3.84 ± 0.34* | 1.36 ± 0.03* | 1.78 ± 0.19* | 0.82 ± 0.19 |
| 5 | 3.82 ± 0.72* | 1.33 ± 0.04* | 1.69 ± 0.09* | 0.83 ± 0.03 |
| 2.5 | 5.51 ± 0.35* | 2.51 ± 0.04* | 3.59 ± 0.14* | 0.84 ± 0.04 |
| 1 | 7.45 ± 0.17* | 2.33 ± 0.06* | 2.95 ± 0.08* | 1.05 ± 0.07 |
| Pazopanib | ||||
| 1 | 1.05 ± 0.15 | 0.43 ± 0.06* | 1.01 ± 0.11 | 0.86 ± 0.09 |
| Dabrafenib | ||||
| 100 | 2.49 ± 0.32* | 0.41 ± 0.05* | 1.03 ± 0.09 | 0.28 ± 0.01* |
| 50 | 2.42 ± 0.21* | 0.56 ± 0.05* | 1.69 ± 0.30* | 0.44 ± 0.10* |
| 30 | 2.22 ± 0.24* | 0.71 ± 0.03* | 1.52 ± 0.12* | 0.59 ± 0.07* |
| 20 | 1.59 ± 0.05* | 0.90 ± 0.05 | 1.31 ± 0.02* | 0.65 ± 0.01* |
| 10 | 1.35 ± 0.19* | 0.94 ± 0.04 | 1.38 ± 0.13* | 0.97 ± 0.07 |
| Cabozantinib | ||||
| 30 | 1.55 ± 0.06* | 0.94 ± 0.05 | 1.35 ± 0.18* | 0.95 ± 0.05 |
| 20 | 1.30 ± 0.15* | 0.92 ± 0.05 | 1.24 ± 0.05* | 0.94 ± 0.06 |
| 10 | 1.46 ± 0.08* | 1.01 ± 0.03 | 1.23 ± 0.11* | 1.03 ± 0.01 |
| Ruxolitinib | ||||
| 100 | 0.71 ± 0.08* | 0.28 ± 0.06* | 1.17 ± 0.12 | 0.99 ± 0.03 |
| 50 | 0.97 ± 0.20 | 0.49 ± 0.06* | 1.07 ± 0.07 | 0.87 ± 0.08 |
| 30 | 1.00 ± 0.09 | 0.54 ± 0.02* | 1.08 ± 0.09 | 1.05 ± 0.11 |
| 20 | 0.81 ± 0.05 | 0.62 ± 0.05* | 1.00 ± 0.14 | 0.90 ± 0.13 |
| Ceritinib | ||||
| 100 | 0.50 ± 0.06* | 0.08 ± 0.02* | 0.17 ± 0.10* | 0.03 ± 0.02* |
| 50 | 1.21 ± 0.12* | 0.55 ± 0.03* | 0.77 ± 0.07* | 0.45 ± 0.08* |
| 30 | 1.12 ± 0.13 | 0.88 ± 0.05 | 0.70 ± 0.12* | 0.41 ± 0.18* |
| Imatinib | ||||
| 100 | 0.90 ± 0.12 | 0.70 ± 0.11* | 1.04 ± 0.06 | 0.93 ± 0.07 |
| 50 | 0.90 ± 0.06 | 0.67 ± 0.03* | 0.99 ± 0.06 | 0.90 ± 0.01 |
| 30 | 0.93 ± 0.04 | 0.71 ± 0.02* | 0.98 ± 0.02 | 0.94 ± 0.04 |
| Lenvatinib | ||||
| 100 | 1.06 ± 0.06 | 0.74 ± 0.04* | 1.07 ± 0.03 | 0.99 ± 0.03 |
| 50 | 0.93 ± 0.01 | 0.70 ± 0.02* | 0.96 ± 0.03 | 0.90 ± 0.01 |
| 30 | 0.95 ± 0.06 | 0.76 ± 0.05* | 0.94 ± 0.01 | 0.86 ± 0.04 |
| Idelalisib | ||||
| 100 | 1.13 ± 0.05 | 0.66 ± 0.03* | 1.05 ± 0.01 | 0.65 ± 0.03* |
| 50 | 1.00 ± 0.08 | 0.76 ± 0.04* | 0.97 ± 0.04 | 0.83 ± 0.06 |
| Crizotinib | ||||
| 100 | 0.97 ± 0.14 | 0.86 ± 0.15 | 1.09 ± 0.12 | 0.80 ± 0.08* |
The signal from DMSO-treated samples was set as 1. * p < 0.05 as compared to DMSO-treated samples. The next lower concentrations showed no effects. KIs not listed also showed no effects